Fig. 9: Model for the role of p62 and NBR1 in the regulation of PPARγ:RXRα heterodimerization and PPARγ-mediated thermogenic program in brown adipocytes.
From: NBR1 is a critical step in the repression of thermogenesis of p62-deficient adipocytes through PPARγ
p62 and NBR1 translocate into the nucleus of brown adipocytes upon adrenergic stimulation and form a multi-protein complex with the nuclear receptor PPARγ and its obligate co-activator RXRα. p62 separately interacts with PPARγ and RXRα, increasing their nuclear proximity and facilitates their heterodimerization to drive thermogenic gene expression. NBR1 emerges as an opposite player that impairs PPARγ:RXRα complex formation and decreases PPARγ activity through direct interaction with PPARγ. The fact that p62 and NBR1 synergistically bind to PPARγ allows p62 to restrain NBR1 from its inhibitory binding to PPARγ. Nuclear p62 serves as a thermogenic promoter contributing to PPARγ activation in brown adipocytes.
